Staying healthy in Japan

JAPANESE FOUNDATION FOR CANCER RESEARCH CANCER CHEMOTHERAPY CENTER

Many of you know of my struggles with the Japanese lan­guage for these last eight years, since I arrived in Japan. Well, despite the frustrations and my general low ability in Nihongo, I m glad to say it’s finally paid off. At least in one sense. Through a Japanese conversa­tion class with a group of women in the CWAJ (College Women’s Association of Japan), I met the delightful Michiko Tsukagoshi.

Besides being friendly and helpful in the language, I im­mediately felt a kinship with Michiko because she was inter­ested in talking (in Japanese, of course, although she also speaks good English) about health and medicine.

It was only later that I learn­ed her husband., Shigeru Tsukagoshi, M.D., Ph.D., was head of the Cancer Chemotherapy Center which is part of the overall body — The Japanese Foundation for Cancer Re­search. He’s as delightful a person as his wife, with im­pressive professional creden­tials as well. He has a M.D. and Ph.D. from Tokyo University, and he was a Re­search Associate at the Univer­sity of Pennsylvania (1960-1963), and in Geneva (1967-1968).

He speaks English fluently, attends international medical meetings frequently and works closely with the people at the National Cancer Institute in Maryland.

Recently I met with Dr. Tsukagoshi and he told me about the foundation and his section concerned with chemo­therapy.

JAPANESE FOUNDATION FOR CANCER RESEARCH

A few years ago I profiled the National Cancer Center (in Tsukiji), a government owned organization. The Japanese Foundation for Cancer Re­search, on the other hand, is a private, non-profit foundation similar to organizations such as the well-known Sloan Kettering Memorial Cancer Center in New York City. The Founda­tion was established in 1908 and helped staff the new gov­ernmental cancer institute (in Tsukiji) when it was begun in 1962. They still enjoy a close working relationship with the government organization.

The Foundation has three main sections — 1) The Cancer Institute, 2) The Cancer Institute Hospital, and 3) The Cancer Chemotherapy Center. It also has four other affiliated organizations, which include: the Nurses School, Pharmacy, Mass Survey Center and the School of Cytotechnology (cy­tology is the study of cells, and their basic characteristics and functions).

The goals of the foundation are very simple: to conquer cancer through research, pre­ventive techniques and treat­ment. Funding for the founda­tion comes from three main sources: 1) hospital income, 2) government grants (for research or special projects), and 3) private and corporate grants and gifts.

THE CANCER CHEMO­THERAPY CENTER — THE HISTORY

Let’s first look at this part of the Foundation since I think it is one of the most interesting parts and also is the one of which Dr. Tsukagoshi is As­sociate Director. The Director (also Director of the Cancer Institute) is Dr. Haruo Sugano.

The idea for “The Chemo­therapy Center began in 1966, after there was a large inter­national cancer meeting in To­kyo, with many important sci­entists from around the world attending. The Director of the Cancer Institute at that time. Prof. Toshio Kurokawa. M.D., was the president of that meet­ing, (He died in February of 1988, remaining Honorary Di­rector of the Cancer Institute Hospital and active clinician until his death.)

Both encouragement and funding for the new Chemo­therapy Center were aided by the U.S. National Cancer In­stitute in Bethesda, Maryland. In addition, one of the purposes of the Chemotherapy Center is to encourage the easy exchange of information about cancer drug research and treatment. So, many people from the Japan Center go to the Ameri­can Institute and vice versa.

In fact I saw several notices about lectures scheduled by visiting scientists, and these scientists came not only from the U.S. hut from Europe as well as other countries. (Since the Japan Center helped Korea establish its own center, many scientists from Korea come to study at the center.)

THREE SECTIONS OF THE CHEMOTHERAPY CENTER

In the Cancer Chemotherapy Center, there are three sections:

1) The Division of Clini­cal Chemotherapy.

Because there are no hospi­tal beds in the Chemotherapy Center Building (adjacent to the hospital), (his department is located in the hospital proper. They have 73 of the 511 hospi­tal beds for the chemotherapy unit, and are called the Depart­ment of Clinical Oncology at the hospital.

The purpose of the clinical division is to conduct both ex­perimental and clinical studies. It is very important that the clinical and experimental branch of the center work together very closely so that new drugs can be clinically tested for efficacy and safety. By the exchange of clinical and research information, hopefully more effective cancer drugs can be introduced.

With advanced cancers, usu­ally cancer drug therapy is used post surgically. The clinical center works with many types of cancer pati­ents, but the main emphasis has been on breast cancer (in women), and stomach cancer. Recent­ly, however, lung cancer has been on the increase (due mainly to cigarette smoking), as have been ovarian, prostatic and pancreatic cancer.

Interestingly, it is the tumors called “solid tumors” that are the most difficult to cure and the most difficult to reach with chemotherapy. Simply because they are so dense in nature, they are more difficult to penerate with drugs and other treatment. However, if these same tumors are caught at an early stage, they are smaller and can be much more easily cured with surgery, chemother­apy and other types of treat­ments.

So, early diagnosis is still the real key to survival in the cancer world. Early diagnosis is fairly simple with tumors such as breast tumors because women can palpate those them­selves on monthly self-breast examinations. It becomes more difficult with lung or ovarian cancer, which cannot be easily discovered; often they are de­tected only in advanced stages.

So, special screening, parti­cularly for those who are most at risk (for example, smokers are at a much greater risk for lung cancer), earlier detection could be accomplished.

Dr. Tsukagoshi has one interesting observation regard­ing breast cancer, however. He says they have found it is the intelligent women who tend to put off self-examination or ignore a mass when they do find it. “Because they are so fearful,” he relates. And isn’t that a shame. Hopefully, with the new surgery that removes the lump instead of the entire breast, (particularly when the tumor is discovered early), women will be less afraid to have the condition diagnosed.

In most cases of advanced cancer, intensive chemotherapy treatment after surgery is need­ed to increase the chance for survival. Cancer in advanced cases, unfortunately, tends to recur, and intensive chemother­apy is also used in that treat­ment. Japan has one of the highest rates of stomach cancer in the world (although, for­tunately, it is declining), and advance stomach cancers tend to recur after one, two or three years.

2) The Anti-Cancer Drug Information Office.

This office was set up with funds from the U.S. National Cancer Institute (which still partially funds it) to dissemi­nate information on cancer drugs to scientists and physi­cians throughout Japan.

Not only knowing the proper drug to use in specific can­cers is important, but the proto­col or regimen for the drug or combination of drugs is also vital for the best effect. The office supplies that, and other scientific and technical infor­mation, on anti-cancer drugs.

3) The Division of Experimental Chemotherapy.

I’ve left this very important part of the center until last because I wanted to concentrate on this division. It is not only an interesting and very active division of the center, but I think it is the most exciting part because it is our hope for the future in the difficult and long-term war on cancer.

Before assuming his present position as Associate Director for the Institute, Dr. Tsuka­goshi headed up this division, which is now run by Takashi Tsuruo. Dr. Tsuruo has a Doc­tor’s Degree in Pharmaceutical Science from Tokyo University and was a research associate at St. Louis University and UCLA in the US. His English is ex­cellent.

The experimental division has four main projects, which I will describe below:

1) Overcoming the problem of drug resistance. After the repeated use of anticancer drugs, a tolerance or resistance to the drug occurs. In other words it becomes much less effective or not effective at all. For example, three main anti-cancer drugs, adriamycin, vincristine and actinomycin D, will produce an “expression” on the tumor cell which has been identified as P-glycoprotcin.

Even though these drugs are each very different in structure, this same reaction and result occurs, which reduces the abili­ty of the drug to inhibit or kill the cancer cell. So, they are working to underhand exactly why it occurs and to find ways to eliminate or reduce it.

2) Investigation of new drugs. New drugs are very important since there is still no single drug or even groups of drugs known today that will cure all cancers. Drug “candidates” (substances that are thought to have the potential for becoming good anti-cancer drugs) are sent from all over Japan, mainly by university and and company scientists. Last year the center tested more than 500 such substances.

Until five years ago the screening center was totally funded by the U.S. National Cancer Institute but, because of budget cutting, they now continue the program with their own funds.

Primary testing for the sub­stances is against mice leuke­mia, because this type of tumor responds to most presently effective anti-cancer drugs. If the substance appears to have some anti-tumor ability, it is then screened against other mice tumors. Finally, it can be screened using nude mice.

Nude mice are a “very strange mice” (in the words of Dr. Tsukagoshi) since they are a type of mice with a defective gene which allows them to actually grow transplanted hu­man tumors. (With normal mice you can only transplant other “mice tumors.”) This is a very good screening process; however, these mice are very expensive because they have very small litters due to their being defective.

3) Investigating Biological Response Modifiers (BRM). Biological Response Modifiers are an exciting new frontier in the fight against cancer. These are substances that will help cancer drugs become more specific and more effective. The idea came from the U.S. National Cancer Institute in 1980, and the Japan Center has been working on BRM since.

Interferon is perhaps the best known of BRMs, and the Japan center is currently work­ing on both Alpha and Beta Interferon.

Since there are substances in the body that react to the in­vasion of any substance (cancer cells included) the idea is to use such substances to target the chemotherapeutic agent to the specific tumor. There are different ways of doing this.

One way is by conjugating (combining) the anti-cancer drug with lymphocytes (white blood cells) which are stimu­lated by the immune system to attack the tumor cells. Cyto­kines are such antigens that are currently under investigation.

4) Understanding the pharmacology of drugs. Pharmacology, or investigating the fate of the drug in the body, is an important part of the investigative process. In drug development, knowing the exact mode of action in the body, and how the drug breaks down and is then eliminated from the body, is vital if effective new compounds are to be found, or older products are to be more effectively used.

The 40-50 scientists, re­searchers, clinicians and staff associated with the Cancer Chemotherapy Center are an impressive bunch. In another column I’ll profile the Cancer Institute Hospital itself and the special Mass Screening program the center has underway.